Disease progression parameters and uses thereof for evaluating multiple sclerosis

Abstract

Methods, systems and kits to detect and/or quantify disease progression in a subject having a progressive form of MS are disclosed.

Description

RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 682,521, filed Aug. 13, 2012, the contents of which are incorporated herein by reference in their entirety.BACKGROUND OF THE INVENTION[0002]Multiple sclerosis (MS) is an inflammatory disease of the brain and spinal cord characterized by recurrent foci of inflammation that lead to destruction of the myelin sheath. In many areas, nerve fibers are also damaged. Inflammatory activity in MS patients tends to be highest in the initial phase of disease.[0003]Emerging data demonstrate that irreversible axonal loss occurs early in the course of MS. Transected axons fail to regenerate in the central nervous system (CNS) and therefore, early treatment aimed at suppressing MS lesion formation is of paramount importance. As early as disease onset, axons are transected in lesions with active inflammation (Trapp et al. (1998) N Engl J Med 338: 278-285; Bjartmar et al. (2001) Curr Opin Neurol 14: 27...

AI Technical Summary

Benefits of technology

[0005]The present invention provides, at least in part, methods, systems and kits for the identification, assessment and / or treatment of a subject having a neurological disorder such as multiple sclerosis (MS), e.g., a progressive form of MS. In one embodiment, the methods, systems and kits include the step of detecting and / or quantifying sustained disease progression (or improvement) in the subject (e.g., a subject with primary or secondary progressive multiple sclerosis (PPMS or SPMS, respectively), or a subject with progressive-relapsing MS (PRMS), by acquiring a value of disease status or progression (also referred to individually herein as “disease status value” or “disease progression value,” respectively, or collectively as “disease status or progression value”). In one embodiment, the disease status or progression value includes a measure of one or more of upper extremity function, lower extremity function, and / or ambulatory function (e.g., short and / or longer distance ambulatory function). The disease status or progression value can further include other MS evaluating methodologies, such as the Expanded Disability Status Scale (EDSS). Scoring systems for facilitating data collection and calculation of assessment values, e.g., for an EDSS score, are also disclosed. Thus, the methods, systems and kits disclosed herein provide several advantages over existing methodologies, including, but not limited to, increased sensitivity in the higher EDSS range; increased responsiveness to worsening in non-long distance ambulatory functions; automated execution of scoring methodologies; improved scoring accuracy and consistency; and decreased problems inherent to the EDSS scale due to, e.g., random variation, lack of linearity, measurement errors, and interpretation errors in scoring.

Problems solved by technology

In many areas, nerve fibers are also damaged.

The loss of oligodendrocytes leads to a reduction in the capacity to re-myelinate and may result in the loss of trophic factors that support neurons and axons (Bjartmar et al.

However, the EDSS alone is typically insufficient to investigate therapeutic efficacy in progressive forms of MS due to, at least, its limited sensitivity in the higher EDSS range where it measures mostly long distance ambulation; a lack of responsiveness to worsening in non-ambulatory functions; and problems inherent to the EDSS scale due to, e.g., random variation, lack of linearity, and measurement errors.

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